title: The involvement of NLRX1 and NLRP3 in the development of nonalcoholic steatohepatitis in mice.
abstract: BACKGROUND
  Increasing evidence suggests that innate immunity is involved in the development of nonalcoholic fatty liver disease. Nod-like receptors (NLRs) have recently been identified as key mediators of inflammatory and immune responses. The aim of this article is to explore the correlation of nucleotide-binding oligomerization domain (NOD)-like receptor (NLR)X1 and NLRP3 with nonalcoholic steatohepatitis (NASH) in mice.
  
  
  METHODS
  In our study, a high-fat diet, lipopolysaccharides (LPSs), and normal diet were given to C57BL mice to establish high fat (HF), HF + LPS, and control groups. Thereafter, serum alanine and aspartate aminotransferase (ALT and AST) levels were measured, and NASH severity was histologically examined. We measured tumor necrosis factor (TNF)-α levels by enzyme-linked immunosorbent assay, protein expression by Western blotting, and mRNA expression by real-time fluorescent quantitative reverse transcription-polymerase chain reaction.
  
  
  RESULTS
  Levels of ALT and AST were higher in HF + LPS mice than in HF mice (p < 0.05). NLRX1 mRNA and protein expression was lower in HF and HF + LPS mice than in control mice (p < 0.05). NLRP3 mRNA expression was higher in HF and HF + LPS mice than in control mice (p < 0.05). The mRNA and protein expression of TNF receptor-associated factor (TRAF)6, interleukin-1β, caspase-1, and apoptosis-associated speck-like protein were significantly higher in HF + LPS mice than in control and HF mice; furthermore, mRNA expression was higher in HF mice than in control mice (p < 0.05), but protein expression was similar.
  
  
  CONCLUSIONS
  NLRX1 and NLRP3 inflammasomes may be important in NASH development.
authors.affiliation: Department of Gastroenterology, Shanghai Changning Central Hospital, Shanghai, China.
authors.forename: Yu-Gang
authors.initials: YG
authors.lastname: Wang
authors.forename: Wen-Li
authors.initials: WL
authors.lastname: Fang
authors.forename: Jue
authors.initials: J
authors.lastname: Wei
authors.forename: Ting
authors.initials: T
authors.lastname: Wang
authors.forename: Na
authors.initials: N
authors.lastname: Wang
authors.forename: Jia-Li
authors.initials: JL
authors.lastname: Ma
authors.forename: Min
authors.initials: M
authors.lastname: Shi
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002352:Carrier Proteins / Q000032:analysis* / Q000502:physiology; D004797:Enzyme-Linked Immunosorbent Assay; D005234:Fatty Liver / Q000209:etiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D024101:Mitochondrial Proteins / Q000032:analysis* / Q000502:physiology; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D065626:Non-alcoholic Fatty Liver Disease; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D002352:Carrier Proteins; D024101:Mitochondrial Proteins; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C555655:NLRX1 protein, mouse; C492716:Nlrp3 protein, mouse
keywords: C57BL mouse; NLRP3; NLRX1; nonalcoholic steatohepatitis